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实验性静脉移植物中肌内膜增生的形成及细胞因子的产生

Formation of myointimal hyperplasia and cytokine production in experimental vein grafts.

作者信息

Sterpetti A V, Cucina A, Lepidi S, Randone B, Corvino V, D'Angelo L S, Cavallaro A

机构信息

I Department of Surgery, University of Rome La Sapienza, Italy.

出版信息

Surgery. 1998 Apr;123(4):461-9.

PMID:9551074
Abstract

BACKGROUND

The purpose of this study was to determine the correlation between progression and regression of myointimal hyperplasia (MH) and cytokine production in experimental vein grafts. Although the autologous vein is the best suitable bypass conduit for reconstruction of peripheral arteries, at the end of the first year thrombosis in the coronary and lower extremity circulation ranges from 20% to 50%. Many of these failures are caused by MH.

METHODS

In 76 inbred Lewis rats, a 1 cm long segment of inferior vena cava was inserted at the level of the abdominal aorta. The segments of inferior vena cava were obtained from syngeneic Lewis rats. In 56 animals the arterial vein graft was explanted 3 days (n = 10), 7 days (n = 10), 4 weeks (n = 26), and 12 weeks (n = 10) after operation. In 20 animals the vein graft was explanted 4 weeks after being in the arterial system and reimplanted as iliac venovenous bypass in syngeneic Lewis rats. These grafts were explanted 2 weeks (n = 10) and 8 weeks (n = 10) later. Grafts were analyzed by light and electron microscopy, morphometric study, and histochemical analysis and were put in an organ culture to assess cytokine production.

RESULTS

We observed MH formation in arterial vein grafts and MH regression in reimplanted vein grafts (p < 0.001). MH formation was correlated with production of platelet-derived growth factor, basic fibroblast growth factor, interleukin-1, and tumor necrosis factor-alpha. MH regression was correlated with transforming growth factor-beta 1 production.

CONCLUSIONS

On the basis of the results of our study, we conclude that MH formation in experimental vein grafts depends on production of platelet-derived growth factor, basic fibroblast growth factor, interleukin-1, and tumor necrosis factor-alpha, and MH regression depends on transforming growth factor-beta 1 production. Cytokine therapy may represent a valuable new treatment to prevent vein bypass failures caused by MH.

摘要

背景

本研究的目的是确定实验性静脉移植物中肌内膜增生(MH)的进展与消退和细胞因子产生之间的相关性。尽管自体静脉是重建外周动脉最合适的旁路管道,但在第一年结束时,冠状动脉和下肢循环中的血栓形成率在20%至50%之间。这些失败中有许多是由MH引起的。

方法

在76只近交系Lewis大鼠中,将一段1厘米长的下腔静脉段插入腹主动脉水平。下腔静脉段取自同基因Lewis大鼠。在56只动物中,动脉静脉移植物在术后3天(n = 10)、7天(n = 10)、4周(n = 26)和12周(n = 10)后取出。在20只动物中,静脉移植物在进入动脉系统4周后取出,并在同基因Lewis大鼠中作为髂静脉-静脉旁路重新植入。这些移植物在2周(n = 10)和8周(n = 10)后取出。通过光镜和电镜、形态计量学研究和组织化学分析对移植物进行分析,并将其置于器官培养中以评估细胞因子的产生。

结果

我们观察到动脉静脉移植物中有MH形成,而重新植入的静脉移植物中有MH消退(p < 0.001)。MH的形成与血小板衍生生长因子、碱性成纤维细胞生长因子、白细胞介素-1和肿瘤坏死因子-α的产生相关。MH的消退与转化生长因子-β1的产生相关。

结论

根据我们的研究结果,我们得出结论,实验性静脉移植物中MH的形成取决于血小板衍生生长因子、碱性成纤维细胞生长因子、白细胞介素-1和肿瘤坏死因子-α的产生,而MH的消退取决于转化生长因子-β1的产生。细胞因子治疗可能是预防由MH引起的静脉旁路失败的一种有价值的新治疗方法。

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